Uterine prostaglandins may participate in the regulation of the uterine and systemic circulation during pregnancy. Thus, preliminary experiments from our laboratory have indicated that arterial infusion of angiotensin II results in the rapid release of prostaglandins into uterine venous effluent, which is associated with a significant fall in uterine vascular resistance. The purpose of this proposal is to extend these investigations, in order to define the role that uterine prostaglandins might play in the regulation of systemic blood pressure and uterine blood flow during pregnancy. In pregnant and nonpregnant chloralose anesthetized dogs, we will explore the effects of various experimental interventions (uterine ischemia, carotid occlusion, infusions of angiotensin I and II, bradykinin, norepinephrine) on uterine blood flow and systemic blood pressure. The hemodynamic responses will be related to changes in the prostaglandin content of uterine venous blood. Uterine release of prostaglandins will be continuously monitored using the blood superfused organ technique. In addition, solvent extraction and thin layer chromatography, coupled with parallel bioassay and radioimmunoassay will be used to characterize and determine blood levels of prostaglandins of the E, F and A series. Having defined the conditions which enhance the release of uterine prostaglandins, we will investigate the humoral and hemodynamic consequences of inhibition of prostaglandin synthesis (indomethacin treatment). Possible interactions between prostaglandins, renin-angiotensin and kallikrein-kinin systems will also be investigated by relating simultaneous measurements of plasma renin activity, kinins and prostaglandins in uterine venous blood during various experimental situations. Finally, the patterns of prostaglandin release during gestation in other vascular beds (renal, mesenteric) will be examined and the functional consequences of its alterations defined. We expect, thereby, to define more fully, those humoral elements which may participate in the regulation of blood pressure and uterine circulation during pregnancy.